Microspectroscopy (μFTIR) Reveals Co-localization of Lipid Oxidation and Amyloid Plaques in Human Alzheimer Disease Brains

Abstract

Amyloid peptides are the main component of one of the characteristic pathological hallmarks of Alzheimer's disease (AD): senile plaques. According to the amyloid cascade hypothesis, amyloid peptides may play a central role in the sequence of events that leads to neurodegeneration. However, there are other factors, such as oxidative stress, that may be crucial for the development of the disease. In the present paper, we show that it is possible, by using Fourier tranform infrared (FTIR) microscopy, to co-localize amyloid deposits and lipid peroxidation in tissue slides from patients affected by Alzheimer's disease. Plaques and lipids can be analyzed in the same sample, making use of the characteristic infrared bands for peptide aggregation and lipid oxidation. The results show that, in samples from patients diagnosed with AD, the plaques and their immediate surroundings are always characterized by the presence of oxidized lipids. As for samples from non-AD individuals, those without amyloid plaques show a lower level of lipid oxidation than AD individuals. However, it is known that plaques can be detected in the brains of some non-AD individuals. Our results show that, in such cases, the lipid in the plaques and their surroundings display oxidation levels that are similar to those of tissues with no plaques. These results point to lipid oxidation as a possible key factor in the path that goes from showing the typical neurophatological hallmarks to suffering from dementia. In this process, the oxidative power of the amyloid peptide, possibly in the form of nonfibrillar aggregates, could play a central role.

Pre-plaque conformational changes in Alzheimer’s disease-linked Aβ and APP

“…The β-aggregation level of proteins was studied by calculating the peak intensity ratio between 1,620 and 1,640 cm −1 , corresponding to β-sheet structures and the maximum corresponding mainly to α-helical content at 1,656 cm −1 . An increase in the 1,620–1,640 cm −1 component is considered a signature of amyloid fibrils10111436. We were not able to detect changes in the range of 1,690 cm −1 that were previously described to differentiate antiparallel and parallel Aβ in a study on purified Aβ using FTIR (ref.…”

“…1b–g). This type of intermolecular β-sheet structure has been described as amyloid aggregates in brain tissue samples analysed by μFTIR (refs 11, 14). However, β-sheet content in brain sections of 1-month-old Tg19959 mice was similar to those of wild-type mice.…”

Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans

“…The derivative of each FTIR spectrum was computed and the ratio corresponding to lipid oxidation 1741 cm -1 /2960 cm -1 (COOH/−CH 3 ) was calculated. (Benseny-Cases et al, 2014) Statistical analysis Past 3.03 was used for all statistical analyzes. Statistical significance between two groups was assessed by T tests.…”

Photothermal Microscopy for High Sensitivity and High Resolution Absorption Contrast Imaging of Biological Tissues

“…It is suggested that lipid has a steeper refractive index/temperature slope (5 × 10 −5 -5 × 10 −4 K −1 ), therefore chromophores in lipid results in significant PT signal. Lipid metabolism in brain is closely related to the neurodegeneration such as Alzheimer's disease [49,50]. Therefore, the ability to imaging of both neuron and lipid structure at high spatial resolution will be a powerful technique to study such diseases.…”